Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery

Phase 4

Completed

Conditions: Coronary Artery Bypass
Antiplatelet Agents

Interventions: Drug: Aspirin
Drug: Ticagrelor

Registration Number: NCT02201771

Lead Sponsor: Ruijin Hospital

Brief Summary: The study population will include all patients undergoing elective CABG. Consent and randomization will occur before surgery. Total 500 patients undergoing elective CABG will be randomly assigned into three groups with 1:1:1 ratio(167 patients per group) in this open-label study. All the enrolled patients will stop oral antiplatelet drugs according to local protocol before the surgery. Within the first 24 hours after surgery, study medication should be restarted and continued for 12 months. Arm A will restart oral antiplatelet drugs by giving aspirin 100mg qd, Arm B will also restart oral antiplatelet drugs by giving ticagrelor 90mg bid plus aspirin 100mg qd and Arm C will also restart oral antiplatelet drugs by giving ticagrelor 90mg bid. Treatment will continue for 12 months, at which time patients will undergo a multislice computed tomography angiography to assess vein graft patency.

This study is designed to show the superiority of ticagrelor and ticagrelor plus aspirin as compared with aspirin monotherapy respectively for the 1-year primary efficacy end point of vein graft patency.

Detailed Description: The study is designed to show the superiority of ticagrelor and ticagrelor plus aspirin as compared with aspirin monotherapy respectively for the 1-year primary efficacy end point of vein graft patency. The primary comparison includes two separate parts. One is to demonstrate T+A better than A and the other is T better than A.

One year rate of vein graft patency in the aspirin group is estimated as 80%. The assumed rate of ticagrelor plus aspirin is 90%. With a two-sided alpha level 0.05 and 80% power, 199 grafts to each group are required. On the other hand, if we assume the rate of ticagrelor monotherapy has the 1-year vein graft patency rate of 87%, under the same two-sided 0.05 alpha 441 grafts in each arm will offer 80% power to show the superiority of ticagrelor along for the primary efficacy end point.

Combined the above two assumptions, if the allocation rate is 1:1:1, this study needs to recruit 1,323 grafts in total (441 in each) to achieve the pre-specified power for both the two comparisons (T+A vs. A and T vs. A).

The principle investigator assumes that the average number of the vien grafts in one patient is 2.7-3.0. With this assumption, 500 patients are to be recruited, which will provide us a total of 1350 - 1500 grafts.

According to the above, this study will be a confirmatory clinical trial to the primary endpoint.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 500

Inclusion Criteria

Patients able to provide written informed consent
Provision of informed consent prior to any study specific procedures
Female and male patients aged 18-80 years
Indication for CABG surgery

Exclusion Criteria

Cardiogenic shock, haemodynamic instability
Need for urgent revascularization within 5 days from presentation
Single vessel disease
Two vessel disease with normal left ventricular function (> 50%)
Need for concomitant other cardiac surgery (e.g. valve replacement)
Need for dual antiplatelet treatment for the patients undergoing CABG after acute coronary syndrome(ACS)
Contraindication for aspirin and ticagrelor use(e.g. known allergy)
History of bleeding diathesis within 3 months prior presentation
History of significant GI bleed within 1 year prior presentation
History of peptic ulcer without GI bleeding in past 3 years
History of intracranial hemorrhage
History of moderate to severe liver impairment
Patient requires dialysis
Patient with an increased risk of bradycardic events (as patients without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree arteriolar-venular block or bradycardic-related syncope)
Need vitamin K antagonist therapy after bypass surgery eg. persistent atrial fibrillation, mechanical valves
Known, clinically important thrombocytopenia(i.e. < 100*109/L)
Known, clinically important anaemia (i.e. <100g/L)
Participation in another investigational drug or device study in the last 30 days
Pregnancy or lactation(for premenopausal women 2 methods of reliable contraception, one of which must barrier method, are required)
Concomitant oral or intravenous therapy with strong cytochrome P450 3A4(CYP3A4) inhibitors, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers which cannot be stopped for the course of the study (strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, over 1 litre daily of grapefruit juice. Substrates with narrow therapeutic index: cyclosporine, quinidine. Strong inducers: rifampin, phenytoin, carbamazepine. )
Any other condition such as active cancer
Life expectancy less than 12 months that may result in protocol non-compliance or a risk for being lost to follow up
Indication for major surgery(e.g. cancer treatment, carotid surgery, cerebral surgery, major vascular surgery)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aspirin	Aspirin	aspirin 100mg tablet by mouth daily for 12 months
Ticagrelor plus Aspirin	Ticagrelor	ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months
Ticagrelor plus Aspirin	Aspirin	ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months
Ticagrelor	Ticagrelor	ticagrelor 90mg tablet by mouth twice daily for 12 months

Primary Outcome Measures

Name	Time	Method
The Patency of Saphenous Vein Grafts	up to 12 months	assessed by multislice computed tomography angiography (MSCTA) or coronary angiography(CAG). FitzGibbon grade A (stenosis \<50%) is defined as "patency".

Secondary Outcome Measures

Name	Time	Method
The Number of Major Adverse Cardiovascular Event (MACE)	up to 12 months	MACE, composite of CV death, myocardial infarction or stroke (ischaemic or unknown etiology)
The Patency of Saphenous Vein Grafts	up to 7 days	assessed by MSCTA or CAG. FitzGibbon grade A (stenosis \<50%) is defined as "patency".
The Rate of Post-operative Atrial Fibrillation After CABG.	up to 7 days	Number of Participants with Post-operative Atrial Fibrillation after CABG
The Rate of Freedom From Angina According to Canadian Cardiovascular Society (CCS) Classification	up to 12 months	Number of Participants Free of Angina per CCS Classification
Number of the Major Bleeding Events	up to 12 months	According to modified TIMI criteria, the "Major Bleeding Events" is defined as the combination of CABG-related bleeding and non-CABG-related major bleeding(Intracranial bleeding, Clinically overt signs of hemorrhage with hemoglobin drop ≥5 g/dL and Fatal bleeding).

Trial Locations

Locations (6): Xinhua Hospital, Shanghai Jiaotong University School of Medicine
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Shanghai, Shanghai, China
Nan Jing First Hospital
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Nanjing, Jiangsu, China
Henan Provincial People's Hospital
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Zhengzhou, Henan, China
Jiangsu Province Hospital
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Nanjing, Jiangsu, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
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Shanghai, Shanghai, China
Changhai Hospital of Shanghai
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Shanghai, Shanghai, China